Precision Quality Check of Immunotherapeutics via Single Cell Cytokine Mapping

Despite the demonstrated benefit of CD targeted CAR T immunotherapeutics two challenges remain to bringing the therapeutics to market The first key challenge is to reproducibly manufacture the therapy so that the cellsandapos cytokine mediated function acts in a predictably consistent fashion post manufacturing The second key challenge is to manage the cellandapos s adverse effect immuno toxicity namely cytokine release syndrome CRS of IL and other inflammatory cytokines while also ensuring efficacy against the CD target A more effective pre infusion quality control test to ensure consistent and safe functioning would be not only address these two critical challenges but help pharmaceutical firms satisfy FDA concerns in both of these areas Such a test would have deep impact on ensuring the pharmas help these therapies to market and in making sure that patients in need with incurable B cell malignancies have access to these revolutionary therapies A more reliable in vitro CAR T functional test would allow physicians to remove or modify the inconsistent or unsafe cell therapies prior to injection significantly reducing risk to the patient and improving odds of therapeutic success However the current leading pre infusion tests do not address the most important clinical requirements The first requirement of such a test is to evaluate the CAR functional cell cytokine activation in the single cell poly functional cell subsets a correlate of quality immune response and also monitor for adverse functional reactions amongst these cell subsets That requires up to non overlapping cytokines per cell A second requirement is to measure the cellsandapos true secretions in an ex vivo manner rather than fixing the cells and manipulating their true function IsoPlexisandapos microchip technology meets these two needs for the first time It measures the range of efficacy polyfunctional cytokine markers anti tumor stimulatory chemotactic while measuring the CRS related inflammatory and also regulatory cytokines from those subsets up to cytokines per cell It does so in an ex vivo platform that not only measures true cell secretion to CD target but can also interact with and respond to the target cell directly on device IsoPlexis plans to use its core technology and learning to create an in vitro assessment test to measure for consistent range of function for in CAR T cell therapies and to monitor for markers of safety and efficacy We propose to do the following specific aims Develop a panel and reproducible assay for measurement of CD CAR cells upon interaction with CD immobilized to ensure consistent function to CAR target Implement the assay above with transfected CAR T donor samples and demonstrate a clinically useful workflow With the Phase I award support we expect in the future to use it as a companion diagnostics tool to monitor the response of patients and ensure proper management of these personalized living drugs in every patient justifying the broad impact of the proposed microdevice in immune oncology Despite the demonstrated benefit of emerging cancer immunotherapeutics their adverse effect e g immunotoxicity is a major concern and could be potentially life threatening We propose to further develop and validate our single cell cytokine mapping device and use it as a working platform to quality check the T cells immune effector function immunotoxity during CAR T treatment along with our pharmaceutical and academic partners In the future we expect to use our device as a companion diagnostics tool to monitor the response of patients and ensure proper management of these personalized living drugs in every patient which has a broad impact in immuno oncology